Processes that are known or thought to be useful for the production of an optically active β-hydroxycarboxylic acid derivative include (1) once synthesizing a racemic form of a desired β-hydroxycarboxylic acid derivative, followed by optical resolution using an optically active resolving agent or an enzyme, (2) starting with an asymmetric compound, or (3) using an asymmetric catalyst.
The process (1) is exemplified by a process using an enzyme to achieve optical resolution of a racemate. For example, only one of the optical isomers of a racemic esterified β-hydroxycarboxylic acid derivative may selectively be hydrolyzed by using lipase.
The process (1) which uses an optically active resolving agent requires an equivalent or more amount of a resolving agent relative to a β-hydroxycarboxylic acid derivative. Moreover, complicated procedures such as crystallization, separation, and purification, are involved before obtaining an optically active β-hydroxycarboxylic acid derivative. The process (1) which uses an enzyme, while capable of yielding a β-hydroxycarboxylic acid derivative with relatively high optical purity, limits the type of a reaction substrate and the absolute configuration of a resulting β-hydroxycarboxylic acid derivative.
The process (2) is conceivable but problematic in that an optically active starting compound is not only expensive but must be used in a stoichiometric excess.
As the process (3), detailed researches have recently been done into catalytic asymmetric synthesis of an optically active β-hydroxycarboxylic acid derivative that can achieve high efficiency and asymmetric yield. For example, U.S. Pat. No. 4,933,482A discloses a process of preparing an optically active β-hydroxycarboxylic acid derivative. The process comprises asymmetrically hydrogenating a β-keto compound using a 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl)ruthenium complex (BINAP-Ru catalyst). The process is very useful in that a β-hydroxycarboxylic acid derivative having high optically purity can be prepared under mild conditions. However, the process involves reacting for a relatively long time such as several tens of hours under a hydrogen pressure of 5 to 40 atm.